Methyl iodide → Methyl 1-methyl-4-(trifluoromethyl)cyclohexanecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (22.0 mL, 124.0 mmol) in tetrahydrofuran (60 mL) was added n-BuLi (2.0 M solution in hexane, 59.0 mL, 95.0 mmol) at 0° C. and the reaction mixture was allowed to stir at same temperature for 20 minutes before cooled to −78° C. Methyl 4-(trifluoromethyl)cyclohexanecarboxylate (10.0 g, 48.0 mmol) in tetrahydrofuran (60 mL) was added dropwise at −78° C. The reaction mixture was stirred at same temperature for 2 hours and then neat methyl iodide (4.5 mL, 72.0 mmol) was added dropwise. After stirring at −78° C. for 1 hour, the reaction mixture was warmed to ambient temperature and stirred for 16 hours, before quenched with 25% aqueous ammonium chloride solution (100 mL) at 0° C. and extracted with ethyl acetate. The organic layer was washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo to afford the title compound (11.2 g, 99%) as a brown colored oil: 1H NMR (300 MHz, CDCl3) δ 3.70 (s, 3H), 2.32-2.28 (m, 2H), 2.01-1.80 (m, 3H), 1.42-1.08 (m, 7H).

Provenance & Evidence